TY - JOUR
T1 - Secukinumab in the Treatment of Moderate-to-Severe Hidradenitis Suppurativa
T2 - Pooled Pharmacokinetics and Safety Results From the SUNSHINE and SUNRISE Phase 3 Studies
AU - Alavi, Afsaneh
AU - Reguiai, Ziad
AU - Jemec, Gregor B E
AU - Gottlieb, Alice B
AU - Wozniak, Magdalena B
AU - Uhlmann, Lorenz
AU - Fan, Heng
AU - Llobet Martinez, Angela
AU - Bruin, Gerard
AU - Thomas, Nicolas
AU - Alarcon, Ivette
AU - Bieth, Bruno
AU - Ravichandran, Shoba
AU - Kimball, Alexa B
N1 - © 2025 The Author(s). International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.
PY - 2026/2
Y1 - 2026/2
N2 - BACKGROUND: Secukinumab, a fully human, monoclonal antibody targeting interleukin-17A, is approved for moderate-to-severe HS in adults. This study evaluated pharmacokinetics (PK), high-sensitivity C-reactive protein (hsCRP) changes, and safety of secukinumab over 52 weeks in SUNSHINE and SUNRISE Phase 3 trials.METHODS: An exploratory analysis of pooled Phase-3 trials evaluated serum PK and safety of secukinumab 300 mg every 2 (SECQ2W) or 4 weeks (SECQ4W). A population PK model assessed the effects of body weight, disease severity, and baseline hsCRP on secukinumab serum concentration. Exposure-response analysis assessed the relationship between predicted PK and HS clinical response [HiSCR]. No confirmatory statistical testing was performed.RESULTS: Mean serum trough concentration at Weeks 16, 24, and 52 was ~2-fold higher with SECQ2W vs. SECQ4W. At Week 16, exposure overlap was high, with an estimated numerical increase in HiSCR of ~3% for SECQ2W over SECQ4W. At Week 52, HiSCR levels plateaued. At Week 16, hsCRP decreased from 18.6 ± 26.3 mg/L to 12.8 ± 18.0 mg/L (SECQ2W), 15.9 ± 27.6 mg/L to 11.5 ± 18.4 mg/L (SECQ4W), and remained unchanged with placebo (14.4 ± 22.5 mg/L to 14.7 ± 23.8 mg/L); reductions were sustained through Week 52. Higher body weight, disease severity, and baseline hsCRP were associated with lower secukinumab serum concentrations. Secukinumab immunogenicity was low (< 1%), with no new safety signals.CONCLUSION: Secukinumab serum concentrations in patients with HS varied with body weight, disease severity, and baseline hsCRP. SECQ2W may benefit certain patients. Secukinumab reduced hsCRP through Week 52. The safety profile of secukinumab was consistent with other approved indications, with no apparent dose-response relationship observed.TRIAL REGISTRATION: NCT03713619 (Novartis study code CAIN457M2301). NCT03713632 (Novartis study code CAIN457M2302).
AB - BACKGROUND: Secukinumab, a fully human, monoclonal antibody targeting interleukin-17A, is approved for moderate-to-severe HS in adults. This study evaluated pharmacokinetics (PK), high-sensitivity C-reactive protein (hsCRP) changes, and safety of secukinumab over 52 weeks in SUNSHINE and SUNRISE Phase 3 trials.METHODS: An exploratory analysis of pooled Phase-3 trials evaluated serum PK and safety of secukinumab 300 mg every 2 (SECQ2W) or 4 weeks (SECQ4W). A population PK model assessed the effects of body weight, disease severity, and baseline hsCRP on secukinumab serum concentration. Exposure-response analysis assessed the relationship between predicted PK and HS clinical response [HiSCR]. No confirmatory statistical testing was performed.RESULTS: Mean serum trough concentration at Weeks 16, 24, and 52 was ~2-fold higher with SECQ2W vs. SECQ4W. At Week 16, exposure overlap was high, with an estimated numerical increase in HiSCR of ~3% for SECQ2W over SECQ4W. At Week 52, HiSCR levels plateaued. At Week 16, hsCRP decreased from 18.6 ± 26.3 mg/L to 12.8 ± 18.0 mg/L (SECQ2W), 15.9 ± 27.6 mg/L to 11.5 ± 18.4 mg/L (SECQ4W), and remained unchanged with placebo (14.4 ± 22.5 mg/L to 14.7 ± 23.8 mg/L); reductions were sustained through Week 52. Higher body weight, disease severity, and baseline hsCRP were associated with lower secukinumab serum concentrations. Secukinumab immunogenicity was low (< 1%), with no new safety signals.CONCLUSION: Secukinumab serum concentrations in patients with HS varied with body weight, disease severity, and baseline hsCRP. SECQ2W may benefit certain patients. Secukinumab reduced hsCRP through Week 52. The safety profile of secukinumab was consistent with other approved indications, with no apparent dose-response relationship observed.TRIAL REGISTRATION: NCT03713619 (Novartis study code CAIN457M2301). NCT03713632 (Novartis study code CAIN457M2302).
KW - C-reactive protein
KW - Biological products
KW - Hidradenitis suppurativa
KW - Interleukin-17
KW - Monoclonal antibodies
KW - Severity of Illness Index
KW - Body Weight
KW - Humans
KW - Middle Aged
KW - Hidradenitis Suppurativa/drug therapy
KW - Interleukin-17/antagonists & inhibitors
KW - Male
KW - Treatment Outcome
KW - Antibodies, Monoclonal, Humanized/pharmacokinetics
KW - Clinical Trials, Phase III as Topic
KW - Female
KW - Adult
KW - C-Reactive Protein/metabolism
U2 - 10.1111/ijd.70025
DO - 10.1111/ijd.70025
M3 - Article
C2 - 40839197
SN - 0011-9059
VL - 65
SP - 289
EP - 298
JO - International Journal of Dermatology
JF - International Journal of Dermatology
IS - 2
ER -